Synthesis from Penicillamine

The use of Trt-protected 3-iodoalanines for lanthionine synthesis is also a highly promising method for the synthesis of 3-methyl- and 3,3-dimethyllanthionines. 40 This method is based on the use of A-trityl-3-iodoalanine benzyl ester (54) and the symmetrically protected bis(Boc)-cystine-derivative dimethyl esters derived from L-t/treo-3-methylcysteine and d-penicillamine. Yields of the respective lanthionine derivatives are >80% however, enantiomeric excesses have not been determined for the 3-substituted lanthionines (Scheme 18). 

This synthesis requires the separation of the diastereoisomers of 92 (obtained from D-penicillamine). An attempt to control the stereochemistry was developed by the Merck group in 1974, in a total synthesis based on the [2+2] cycloaddition of the ketene derived from azidoacetyl chloride and the chiral thiazoline 94. The reaction only gives the /ra .r-pcnam derivative 95, which could be epimerized via the Schiff base 96 (cisltrans ratio = 2 1) (Scheme 51). The separated tyr-isomcr has been transformed into synthetic penicillin G <1974JOC437>. 

Hashimoto K, Singer K, Lazarus GS. Penicillamine-induced pemphigus. Immunoglobulin from this patient induces plasminogen activator synthesis by human epidermal cells in culture mechanism for acantholysis in pemphigus. Arch Dermatol 1984 120(6) 762-4. 

The dihydrothiazine 105b has also been prepared from D-penicillamine and methyl 2-chloro-3-oxopropionate. In principle, its synthesis may involve a cyclization of type 93 or the dehydration of an intermediate of... 

Lead (tap water, leaded paint chips, herbal remedies, gas-sniffing, glazed kitchenware, etc.) Acute N and V, GI distress and pain, malaise, tremor, tinnitus, paresthesias, encephalopathy (red or black feces) Chronic multisystem effects—anemia (X heme synthesis), neuronathv (wrist dronL nephropathy (proteinuria, failure), hepatitis, mental retardation (from pica), >1 fertility and 1 stillbirths Decontamination—gastric lavage + dimercaprol (severe) or EDTA or succimer (penicillamine if unable to use dimercaprol or succimer) Children succimer PO... 

Discuss the synthesis of phenoxy methyl penicillin from tert- 3uty -a ] a-phthalimidom-alonalhydate and D-penicillamine. 

An early form of therapy involves eliminating the substrate either by excluding the substrate from the diet, as in phenylketonuria, or by administering drugs—such as penicillamine in Wilson s disease or allopurinol in gout. Orotic aciduria can be corrected by the administration of uridine, which provides the substrate for the biosynthesis of the nucleosides used in RNA and DNA synthesis and is also a substrate for the biosynthesis of inhibitors of the carbamyl aspartate synthetase, the first enzyme in the formation of orotic acid. By this feedback inhibition, the levels of orotic acid in the urine are reduced by the administration of uridine. 

D-Penicillamine, (CH3)2-CSH-CH -NH2-C02H, which was the first degradation product to be obtained from penicillin and is one of the starting materials for total chemical synthesis, plays no part in the biosynthesis of the penicillin molecule and does not appear to be formed in nature as an independent unit. 

In attempting to crystallize crude penicillamine hydrochloride from hot acetone I found that it reacted with the solvent to yield a crystalline thiazolidine. It was thus a p-thiol-a-amino acid. In the Dyson Perrins Laboratory John Comforth deduced from low Kuhn-Roth C—Me values that it contained a gem-dimethyl group and proved by synthesis in October 1943 that it was p-thiol-D-valine. 

Synthesis. Penicillin G, identical with the natural penicillin G, was synthesized from d-penicillamine and 2-benzyl-4-methoxymethylene-5(4)-oxazolone in a yield of about 0.1% (159a). The synthesis could not be used as synthetic proof of structure. The same synthesis has been used to form very small amounts of analogs of penicillin differing from the known varieties in the nature of the substituent groups at position 2 of the thiazoli-dine ring (159a). 

Leonard, N. J., and G. E. Wilson, Jr. Stereospecific Synthesis and Oxidative Transformation of a Synthetic 1,4-Thiazepine from D-Penicillamine. Tetrahedron Letters 1964, 1465. 

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